Cenerimod for Systemic Lupus Erythematosus

(OPUS-1 Trial)

Recruiting at 198 trial locations

Overseen By Viatris Innovation Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Idorsia Pharmaceuticals Ltd.

Must be taking: Antimalarials, Mycophenolate, Azathioprine, Methotrexate

Must not be taking: Beta-blockers, QT-prolonging drugs, Cyclophosphamide, others

Disqualifiers: Pregnancy, CNS lupus, Heart disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines cenerimod to determine if it can reduce symptoms in adults with moderate to severe Systemic Lupus Erythematosus (SLE), a condition where the immune system attacks the body. Participants will continue their usual SLE treatments, with some receiving cenerimod (a new potential drug) and others a placebo, to assess the effectiveness and safety of cenerimod. This trial may suit those with SLE who experience symptoms like joint pain or skin rashes and are already on certain medications for their condition. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications for Systemic Lupus Erythematosus, as it tests cenerimod on top of existing treatments. However, your current medications must be stable for a certain period before joining the trial.

Is there any evidence suggesting that cenerimod is likely to be safe for humans?

Research has shown that cenerimod is generally well-tolerated in studies involving patients with systemic lupus erythematosus (SLE). One study found that cenerimod improved patients' mental and physical health over six months. Although these results are promising, some participants experienced side effects, though specific details were not provided.

Another study examined the long-term safety of cenerimod in adults with moderate to severe SLE symptoms. This indicates that researchers closely monitor for negative effects and are committed to understanding the treatment's long-term impact.

Overall, while cenerimod appears safe for many patients, potential participants should discuss any concerns with their healthcare providers. This discussion will help them understand what to expect and make informed decisions about joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus?

Researchers are excited about cenerimod for systemic lupus erythematosus (SLE) because it offers a new approach by targeting the sphingosine-1-phosphate receptor 1 (S1P1). This mechanism is different from many current treatments like corticosteroids and immunosuppressants, which generally suppress the immune system more broadly. By specifically modulating the S1P1 receptor, cenerimod aims to reduce immune system overactivity while potentially minimizing side effects. This targeted action could lead to better management of SLE with fewer adverse effects, making it a promising candidate in the treatment landscape.

What evidence suggests that cenerimod might be an effective treatment for Systemic Lupus Erythematosus?

Research has shown that cenerimod, which participants in this trial may receive, may help reduce symptoms of Systemic Lupus Erythematosus (SLE). In earlier studies, patients who took cenerimod experienced better mental and physical health compared to those who took a placebo. Cenerimod targets a specific part of the immune system, potentially decreasing disease activity in SLE patients. Although not all study goals were achieved, a noticeable reduction in symptoms was observed. This suggests that cenerimod could be a promising addition to current SLE treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Viatris Innovation GmbH

Are You a Good Fit for This Trial?

Adults with moderate to severe Systemic Lupus Erythematosus (SLE) who have been diagnosed at least 6 months prior and are on stable SLE medications can join. They need a certain level of disease activity and organ involvement, and women must agree to pregnancy tests and use effective contraception. Excluded are those with heart rate issues, certain heart conditions, severe respiratory diseases, liver problems, recent serious cardiovascular events or treatments that could interfere.

Inclusion Criteria

Signed Informed Consent Form (ICF) prior to any study-mandated procedure

I am not pregnant, will test monthly, and will use effective birth control during and 6 months after the study.

My lupus is affecting at least two organs moderately or one organ severely.

Exclusion Criteria

I haven't had B cell-depleting therapy in the last year.

I have severe brain-related lupus symptoms.

I have not taken certain medications recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cenerimod or placebo once daily in addition to background SLE therapy

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cenerimod
• Placebo

Trial Overview The trial is testing Cenerimod's effectiveness in reducing SLE symptoms compared to a placebo over 12 months. It will involve around 420 participants split into two groups: one receiving Cenerimod and the other receiving a placebo pill without active medication.

How Is the Trial Designed?

Group I: Cenerimod 4 mg Experimental Treatment 1 Intervention

Participants will receive cenerimod once daily in addition to background SLE therapy.

Group II: Matching placebo Placebo Group 1 Intervention

Participants will receive matching placebo once daily in addition to background SLE therapy.

Who Is Running the Clinical Trial?

Idorsia Pharmaceuticals Ltd.

Lead Sponsor

Trials

124

Recruited

36,400+

Antonio Olivieri

Idorsia Pharmaceuticals Ltd.

Chief Medical Officer since 2024

Not specified

André C. Muller

Idorsia Pharmaceuticals Ltd.

Chief Executive Officer

Not specified

Viatris Innovation GmbH

Lead Sponsor

Published Research Related to This Trial

Cenerimod, a selective sphingosine 1-phosphate 1 receptor modulator, demonstrated a significant dose-dependent reduction in total lymphocyte count and improved SLE Disease Activity Index scores in patients with systemic lupus erythematosus (SLE) over 12 weeks, indicating its potential efficacy as a treatment.

The study showed that cenerimod had an acceptable safety profile, with similar rates of treatment-emergent adverse events across all doses compared to placebo, and only a minor, temporary decrease in heart rate observed shortly after dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First use of cenerimod, a selective S1P1 receptor modulator, for the treatment of SLE: a double-blind, randomised, placebo-controlled, proof-of-concept study. Hermann, V., Batalov, A., Smakotina, S., et al.[2022]

Cenerimod, a drug being developed for systemic lupus erythematosus, showed similar pharmacokinetics and pharmacodynamics in both white and Asian subjects, indicating that the same dosage can be used for both ethnic groups in future studies.

The drug was found to be safe and well-tolerated, with only one minor adverse event reported, suggesting a favorable safety profile for further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Pharmacodynamics of Cenerimod, A Selective S1P1 R Modulator, Are Not Affected by Ethnicity in Healthy Asian and White Subjects. Juif, PE., Dingemanse, J., Winkle, P., et al.[2022]

Amiselimod, an oral medication for systemic lupus erythematosus (SLE), was generally well tolerated in a phase Ib trial with 17 participants, showing no serious adverse events or significant cardiac effects.

The treatment led to a decrease in anti-double stranded-DNA antibodies and improved SLE disease activity in some patients, suggesting potential efficacy, although low lymphocyte counts were noted as a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amiselimod, a sphingosine 1-phosphate receptor-1 modulator, for systemic lupus erythematosus: A multicenter, open-label exploratory study. Tanaka, Y., Kondo, K., Ichibori, A., et al.[2021]

In a study of 38 Portuguese patients with Systemic Lupus Erythematosus (SLE), belimumab demonstrated significant effectiveness, with SLE Responder Index (SRI) response rates increasing from 51.9% at 6 months to 91.7% at 24 months, indicating a reduction in disease activity.

Belimumab was associated with a good safety profile, with only five patients experiencing adverse events, primarily infections, and the treatment led to a significant decrease in disease activity markers and daily steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab in the treatment of Portuguese Systemic Lupus Erythematosus patients: a real-life multicenter study. Fernandes, BM., Barreira, S., Fonseca, JE., et al.[2021]

In a Phase IIb trial involving 305 patients with systemic lupus erythematosus (SLE), anifrolumab treatment led to a higher rate of achieving the Lupus Low Disease Activity State (LLDAS) compared to placebo, indicating its efficacy in managing SLE symptoms.

The study found that anifrolumab-treated patients not only reached LLDAS earlier but also spent more time in this state, supporting the use of LLDAS as a meaningful endpoint in SLE clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lupus Low Disease Activity State (LLDAS) attainment discriminates responders in a systemic lupus erythematosus trial: post-hoc analysis of the Phase IIb MUSE trial of anifrolumab. Morand, EF., Trasieva, T., Berglind, A., et al.[2019]

Cenerimod, a potential treatment for systemic lupus erythematosus, showed a total mean cumulative recovery of 84% after a single oral dose, primarily excreted in feces (58-100%) with minimal amounts in urine (4.6-12%).

The study identified a significant metabolite, M32, which accounted for 23% of radioactivity in urine and 66% in feces, indicating that while cenerimod itself was primarily excreted in feces, M32 is a key metabolite that may play a role in its pharmacological profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, distribution, metabolism, and excretion of cenerimod, a selective S1P1 receptor modulator in healthy subjects. Boof, ML., van Lier, JJ., English, S., et al.[2020]

In a study of 158 patients with systemic lupus erythematosus, the SLEDAI-2K effectively identified 109 patients who showed overall improvement in disease activity without significant worsening in other areas.

Among the improved patients, only 11 had new laboratory descriptors that were not clinically significant, indicating that the SLEDAI-2K is reliable for assessing true improvements in disease status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLEDAI-2K Does Not Conceal Worsening in a Particular System When There Is Overall Improvement. Touma, Z., Gladman, DD., Su, J., et al.[2015]

Cenerimod, a selective sphingosine-1-phosphate 1 receptor modulator, reaches steady state in approximately 49 days of treatment, with minimal changes in drug exposure after 35 days, indicating a stable pharmacokinetic profile for long-term use.

The incidence of low lymphocyte counts is predicted to be higher in systemic lupus erythematosus (SLE) patients (25.9% for counts below 0.5 × 10^9 cells/L) compared to healthy subjects (18.2%), suggesting a need for monitoring in this population, although dose individualization is not deemed necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modelling pharmacokinetics and pharmacodynamics of the selective S1P1 receptor modulator cenerimod in healthy subjects and systemic lupus erythematosus patients. Lott, D., Juif, PE., Dingemanse, J., et al.[2021]

Cenerimod, a medication being developed for systemic lupus erythematosus, does not significantly affect the pharmacokinetics of the combined oral contraceptive (COC), allowing for safe use during treatment.

In a study with 24 healthy participants, while exposure to levonorgestrel increased slightly (10-25%) with cenerimod, the overall safety profile was good, with only minor adverse events reported, indicating that COC can be safely used alongside cenerimod.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Effect of Cenerimod, a Selective S1P1 Receptor Modulator, on the Pharmacokinetics of a Combined Oral Contraceptive. Juif, PE., Mueller, MS., Charfi, H., et al.[2022]

In a phase III trial with 819 patients, belimumab at 10 mg/kg significantly improved the SLE Responder Index response rate at week 52 compared to placebo (43.2% vs. 33.5%), indicating its efficacy in reducing disease activity in systemic lupus erythematosus (SLE).

Belimumab was generally well tolerated, with serious adverse events being comparable across treatment groups, suggesting that it is a safe addition to standard therapy for SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Furie, R., Petri, M., Zamani, O., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39586304/

Cenerimod, a sphingosine-1-phosphate receptor ... Cenerimod is a selective S1P 1 receptor modulator under investigation for the treatment of systemic lupus erythematosus (SLE).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03742037

Study Details | NCT03742037 | Efficacy and Safety of Four ... The purpose of the study is to assess the efficacy and safety of 4 doses of cenerimod versus placebo in adult subjects with systemic lupus erythematosus (SLE).

3. jrheum.org jrheum.org/content/52/Suppl_1/183.1

EFFECT OF CENERIMOD ON QUALITY OF LIFE IN ... Patients with cenerimod 4 mg groups showed meaning full improvements in the mental and physical components of the SF-36v2 scores compared to placebo at month 6.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02472795

NCT02472795 | Clinical Study to Investigate the Biological ... The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2665991324002467

Cenerimod, a sphingosine-1-phosphate receptor ... Although the primary endpoint was not met after adjustment for multiplicity, treatment with cenerimod 4·0 mg resulted in reduction in SLE disease activity.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06475742

Long-term Safety and Tolerability of Cenerimod in Adults ... The goal of this clinical study is to learn about the long-term safety and tolerability of cenerimod in adult patients with moderate to severe symptoms of ...

7. ard.bmj.com ard.bmj.com/content/annrheumdis/early/2024/11/22/ard-2024-226547/DC7/embed/inline-supplementary-material-7.pdf?download=true

Cenerimod / ACT-334441 Systemic lupus erythematosus ... A Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and tolerability ...